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| Status |
Public on Apr 11, 2020 |
| Title |
Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) [WXS] |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by high throughput sequencing
|
| Summary |
This study demonstrates two fundamental tenets of immunotherapy: vaccines targeting any tumor antigen will not be as effective as those targeting true oncogenic drivers and neither the stimulation of tumor-specific T-cells nor the blockade of a key immune checkpoint is enough to overcome the layers of immune suppression by itself. It provides single cell genetic evidence that vaccination alone generates a population of CD8 T-cells incapable of long-term tumor control due to the activation of numerous immune dysfunction pathways within the tumor. These promising studies have led to the initiation of a Phase II clinical trial testing a novel HER2 vaccine in combination with Pembrolizumab (NCT03632941) to determine if this combination can elicit effective anti-tumor immunity while minimizing off-target immune responses in patients with advanced HER2+ BC.
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| |
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| Overall design |
This novel mouse model is driven by expression of an oncogenic isoform of HER2. To examine the mutation rate and neoepitope formation in these tumors, we performed paired bulk RNAseq/DNAseq of tumors to determine tumor mutational burden and neoepitope profiles in our mice.
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| |
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| Contributor(s) |
Crossby EJ, Acharya CR, Ashby BK |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 10, 2020 |
| Last update date |
Apr 15, 2020 |
| Contact name |
Zachary Conrad Hartman |
| E-mail(s) |
zch@duke.edu
|
| Phone |
919-684-9197
|
| Organization name |
Duke University
|
| Department |
Surgery
|
| Lab |
Lyerly Lab
|
| Street address |
Research Drive MSRB rm 414
|
| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27710 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (20)
|
| GSM4472258 |
WXS: tail rtTA-HER2d16 mouse on FVB background #295 |
| GSM4472259 |
WXS: tail rtTA-HER2d16 mouse on FVB background #297 |
| GSM4472260 |
WXS: tail rtTA-HER2d16 mouse on FVB background #298 |
| GSM4472261 |
WXS: tail rtTA-HER2d16 mouse on FVB background #954 |
| GSM4472262 |
WXS: tumor A rtTA-HER2d16 mouse on FVB background #525 |
| GSM4472263 |
WXS: tumor B rtTA-HER2d16 mouse on FVB background #525 |
| GSM4472264 |
WXS: tumor C rtTA-HER2d16 mouse on FVB background #525 |
| GSM4472265 |
WXS: tumor D rtTA-HER2d16 mouse on FVB background #525 |
| GSM4472266 |
WXS: tumor A rtTA-HER2d16 mouse on FVB background #527 |
| GSM4472267 |
WXS: tumor B rtTA-HER2d16 mouse on FVB background #527 |
| GSM4472268 |
WXS: tumor C rtTA-HER2d16 mouse on FVB background #527 |
| GSM4472269 |
WXS: tumor D rtTA-HER2d16 mouse on FVB background #527 |
| GSM4472270 |
WXS: tumor A rtTA-HER2d16 mouse on FVB background #531 |
| GSM4472271 |
WXS: tumor B rtTA-HER2d16 mouse on FVB background #531 |
| GSM4472272 |
WXS: tumor C rtTA-HER2d16 mouse on FVB background #531 |
| GSM4472273 |
WXS: tumor D rtTA-HER2d16 mouse on FVB background #531 |
| GSM4472274 |
WXS: tumor A rtTA-HER2d16 mouse on FVB background #555 |
| GSM4472275 |
WXS: tumor B rtTA-HER2d16 mouse on FVB background #555 |
| GSM4472276 |
WXS: tumor C rtTA-HER2d16 mouse on FVB background #555 |
| GSM4472277 |
WXS: tumor D rtTA-HER2d16 mouse on FVB background #555 |
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| This SubSeries is part of SuperSeries: |
| GSE148482 |
Stimulation of oncogene-specific tumor infiltrating T-cells through combined vaccine and alpha-PD1 enable sustained anti-tumor responses against established HER2 breast cancer (BC) |
|
| Relations |
| BioProject |
PRJNA624344 |
| SRA |
SRP256208 |
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